The objectives of this research plan are: (a) To identify and quantitate the arachidonic acid metabolites synthesized and released by macrophages at rest, and under various forms of stimulation. (b) To study the regulation of these metabolites in relation to some of the most outstanding functional attributes of the macrophages, namely, adhesion, spreading and phagocytosis. (c) To study the regulation of arachidonic acid metabolites in relation to non-phagocytic stimuli. (d) To study the functional role of arachidonic acid metabolites secreted by macrophages on PMN chemotaxis and lymphocyte regulation. (e) To compare the profile of arachidonic acid metabolism in different macrophage populations. (f) To study the mechanism of phospholipase activation and its relationship with arachidonic acid metabolism. We will label the phospholipid pool of cultured macrophages with 14C-arachidonic acid. By measuring the subsequent release of arachidonic acid metabolites and fatty acids, (by radiochemical methods such as TLC, HPLC and GC), we are able to identify the various arachidonic acid metabolites produced by macrophages, quantitate the amount of their production and to assess the phospholipase activity. The information thus collected will be correlated to the above-mentioned macrophage functions.